L-type calcium channel modulates cystic kidney phenotype

Xingjian Jin, Brian S. Muntean, Munaf S. Aal-Aaboda, Qiming Duan, Jing Zhou, Surya M. Nauli

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

In polycystic kidney disease (PKD), abnormal proliferation and genomic instability of renal epithelia have been associated with cyst formation and kidney enlargement. We recently showed that L-type calcium channel (CaV1.2) is localized to primary cilia of epithelial cells. Previous studies have also shown that low intracellular calcium level was associated with the hyperproliferation phenotype in the epithelial cells. However, the relationship between calcium channel and cystic kidney phenotype is largely unknown. In this study, we generated cells with somatic deficient Pkd1 or Pkd2 to examine ciliary CaV1.2 function via lentiviral knockdown or pharmacological verapamil inhibition. Although inhibition of CaV1.2 expression or function did not change division and growth patterns in wild-type epithelium, it led to hyperproliferation and polyploidy in mutant cells. Lack of CaV1.2 in Pkd mutant cells also decreased the intracellular calcium level. This contributed to a decrease in CaM kinase activity, which played a significant role in regulating Akt and Erk signaling pathways. Consistent with our in vitro results, CaV1.2 knockdown in zebrafish and Pkd1 heterozygous mice facilitated the formation of kidney cysts. Larger cysts were developed faster in Pkd1 heterozygous mice with CaV1.2 knockdown. Overall, our findings emphasized the importance of CaV1.2 expression in kidneys with somatic Pkd mutation. We further suggest that CaV1.2 could serve as a modifier gene to cystic kidney phenotype.

Original languageEnglish (US)
Pages (from-to)1518-1526
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1842
Issue number9
DOIs
StatePublished - Sep 2014
Externally publishedYes

Keywords

  • CaV1.2 L-type calcium channel
  • Cystic kidney
  • Modifier gene
  • PKD
  • Primary cilia

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Fingerprint Dive into the research topics of 'L-type calcium channel modulates cystic kidney phenotype'. Together they form a unique fingerprint.

Cite this